PROJECT SUMMARY Gay, bisexual and other men who have sex with men (MSM) are the group at highest risk of HIV infection in the United States. Pre-exposure prophylaxis (PrEP) has demonstrated high efficacy in preventing HIV infection among MSM. However, uptake in clinical settings has been slow for several reasons, including low awareness and education, low perceived HIV risk, concern for side-effects, and stigma associated with taking the medication. The purpose of the proposed study is to develop and evaluate a brief motivational interviewing (MI) intervention to promote PrEP uptake among MSM during the course of routine HIV screening at a public sexually transmitted disease (STD) clinic. The study will focus on MSM who are at highest risk of incident HIV infection including those who use illicit substances and report condomless sex. Qualitative interviews with HIV-negative, high-risk MSM who have not taken PrEP will inform the initial development of the intervention (Specific Aim 1). Interviews will explore individual- and structural-level facilitators and barriers to PrEP uptake as well as acceptable methods of delivering the intervention. The intervention will then be pilot tested among a small sample (n=15) of high-risk MSM at the public STD clinic (Specific Aim 2). The intervention will consist of a brief MI session, which will include acceptance-based techniques. The initial intervention will take place at the STD clinic (15 minutes), followed by a booster session when STD results are delivered by phone one week later (10 minutes). The intervention will be designed to be feasible and acceptable in a busy clinical setting. After refining the intervention, a small randomized controlled trial (RCT; n=100) will be conducted to assess the impact of the intervention on PrEP uptake relative to an education-only control condition (Specific Aim 3). The goal of the study will be to improve PrEP uptake among a group that is at highest risk of HIV infection. At baseline, one-, and three-month follow-up visits, sexual risk behaviors and substance use will be assessed. Outcomes of the study will include acceptability and feasibility of the intervention as well as preliminary efficacy of increasing PrEP uptake. To measure PrEP uptake, we will evaluate PrEP prescriptions, subsequent retention in care at follow-up visits, and adherence (by self-report and drug levels). The results of this study will inform development of a scalable, novel intervention to promote PrEP uptake among high-risk MSM and will provide the basis for a future R01 efficacy trial.